Thromboelastography with Platelet Mapping Identifies High Platelet Reactivity is Associated with Obesity, Diabetes, and Thrombotic Events.

BACKGROUND: Metabolic comorbidities such as diabetes and obesity are considered pro-inflammatory states which theoretically increase the risk of perioperative thrombotic events across many surgical disciplines. Currently, there is a paucity of objective metrics to determine such risk and ideal pharmacologic targets. Thromboelastography with Platelet Mapping (TEG-PM) provides a comprehensive profile of coagulation and may provide insight into clot dysregulation. METHODS: Patients undergoing lower extremity revascularization underwent serial TEG-PM analysis. The relationship between the TEG-PM metrics and thrombosis was evaluated. Preoperative TEG-PM samples of patients with body mass index (BMI)≥25 were compared to those of patients with a normal BMI, and between patients with diabetes mellitus (DM) and those without. RESULTS: 218 TEG-PM samples from 202 patients were analyzed. The BMI≥25 cohort showed significantly greater platelet aggregation [81.9% (±20.9) vs. 68.6% (±27.7), P < 0.01]. Patients with DM were more frequently on full-dose anticoagulation [47.7% vs. 29.7% P = 0.01] yet demonstrated increased clot strength, or adenosine diphosphate (ADP)-Maximum Clot Amplitude (MA) [49.1 (±16.1) vs. 41.5 (±17.1) and 37.7 (±19.6) vs. 31.6 (±17.4) P < 0.01]. 49 patients experienced thrombosis and exhibited greater platelet aggregation [76.6% (±17.8) vs. 66.8% (±30.4) P = 0.03] and greater ADP/arachidonic acid MA [47.1 (±16.6) vs. 41.9 (±18.8) and 38.2 (±17.8) vs. 32.5 (±19.9) both P = 0.05]. Patients who thrombosed were more often diabetic [69.5% versus 51.0% P = 0.03] and on full-dose anticoagulation [75.0% vs. 56.8% P = 0.02]. CONCLUSIONS: Patients with a BMI≥ 25 and those with diabetes demonstrated TEG-PM profiles similar to patients with thrombosis. Diabetes was independently associated with thrombosis, and full-dose anticoagulation was not protective. This suggests the potential utility of TEG-PM for thrombotic risk stratification based on metabolic factors and suggests antiplatelet agents may be effective at prevention of thrombotic events in this population.

Optimizing platelet inhibition in peripheral artery disease: A comparison of mono-antiplatelet therapy and dual-antiplatelet therapy using thromboelastography.

BACKGROUND: Antiplatelet therapy is used to prevent thrombosis in patients with peripheral artery disease (PAD) following revascularization. However, the current standard of care for these patients remains at the physician's discretion, varying from mono-antiplatelet therapy (MAPT) to dual-antiplatelet therapy (DAPT). Viscoelastic assays such as Thromboelastography with Platelet Mapping (TEG-PM) provide insight into individual coagulation profiles and measure real-time platelet function. This prospective, observational study looks at the differences in platelet function for patients on MAPT versus DAPT using TEG-PM. METHODS: Patients with PAD undergoing revascularization were prospectively evaluated between December 2020 and June 2023. TEG-PM analysis compared platelet function for patients prescribed MAPT (aspirin or clopidogrel) at the initial encounter and DAPT (aspirin and clopidogrel) at the next visit. Platelet function measured in percent inhibition was evaluated at these visits, and within-group t-tests were performed. RESULTS: Of the 195 patients enrolled, 486 samples were analyzed by TEG-PM. Sixty-four patients met the study criteria. At the initial visit, 52 patients had been prescribed aspirin, and 12 patients had been prescribed clopidogrel. For patients initially prescribed aspirin MAPT, an increase of 96.8%in the mean ADP platelet inhibition was exhibited when transitioning to DAPT [22.0% vs. 43.3%, p < .01], as well as an increase of 34.6%in the mean AA platelet inhibition when transitioning to DAPT [60.9% vs. 82.0%, p < .01]. For patients prescribed initial clopidogrel MAPT, an increase of 100% in AA platelet inhibition was exhibited on DAPT compared to the MAPT state [42.3% vs. 84.6%, p < .01]. CONCLUSIONS: Patients on DAPT showed a significant increase in platelet inhibition when compared to initial aspirin MAPT. A significant difference in AA %platelet inhibition was shown for patients on DAPT when compared to initial clopidogrel MAPT. The results show that patients may benefit from DAPT post-revascularization. Personalizing antiplatelet therapy with objective viscoelastic testing to confirm adequate treatment may be the next step in optimizing patient outcomes to reduce thrombosis in PAD patients.

Platelet function testing and clinical outcomes in peripheral arterial disease: Systematic review and narrative synthesis.

OBJECTIVE: This systematic review aims to comprehensively assess the contemporary literature on platelet function testing (PFT) in individuals undergoing revascularization therapy for peripheral arterial disease (PAD). The goal is to identify whether PFT can aid in detecting antiplatelet resistance, predicting post-procedural thrombotic complications, and informing tailored treatment strategies. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature review was conducted using PubMed databases. Search terms included relevant medical subject headings (MeSH) terms. Eligible articles published in English between 1990 and 2023 were analyzed. Studies that examined PFT outcomes in patients with PAD after lower extremity revascularization were included. RESULTS: Ten studies met the inclusion criteria. Various PFT methods were used, including thromboelastography with platelet mapping, multiplate analyzer, Cytochrome P450 2C19 testing, VerifyNow, corrected whole blood aggregometry, platelet function analyzer-100, and light transmission aggregometry. PFT identified individuals who were resistant or non-sensitive to antiplatelet therapy, with such patients facing increased risks of graft/stent thrombosis, amputation, and reintervention. However, substantial heterogeneity in surgical procedures, drug regimens, and testing methods was observed among the studies. CONCLUSIONS: PFTs can play a crucial role in detecting resistance and non-sensitivity to antiplatelet drugs in patients with PAD post-revascularization. However, heterogeneity of data and methods underlines the need for standardized protocols and consensus-building among PFTs. Enhancing clinical utility and reliability could help optimize antiplatelet thromboprophylaxis, minimize thrombotic complications, and improve treatment strategies in vascular surgery. Further research is necessary to solidify the role of PFTs in guiding antiplatelet therapy post-revascularization in patients with PAD.

Impact of Factor Xa Inhibition on Coagulation, Platelet Reactivity, and Thrombosis in Patients with Peripheral Artery Disease.

BACKGROUND: The role of thrombin in vascular pathology is a focus of investigation. The incorporation of direct Factor Xa inhibition into practice patterns is based on its theoretical dual-pathway attenuation of both thrombin generation and platelet aggregation. However, quantification of the effect of direct anti-Xa medications on platelet function is not established. Thromboelastography with platelet mapping (TEG-PM) leverages dual-pathway metrics to provide comprehensive coagulation profiles. We evaluated the effects of direct oral anticoagulants (DOACs) on coagulation and platelet function profiles and correlate these data with postoperative major adverse limb events (MALEs) in patients with PAD. METHODS: We conducted a prospective study of patients undergoing lower extremity revascularization with serial perioperative TEG-PM analysis. Patients on DOACs were compared to those not on DOACs, and stratified by concurrent mono-antiplatelet or dual-antiplatelet regimens (MAPT/DAPT). Postoperative MALE was recorded and difference in antithrombotic regimens and TEG-PM analysis compared between groups. RESULTS: Four hundred seventy-one samples from 141 patients were analyzed. Twenty-nine point five percent were reflective of circulating DOAC therapy. Compared to MAPT alone, patients on DOAC + MAPT exhibited longer time to clot formation (R-time) [7.4 (±2.4) vs. 6.7 (±2.7); P < 0.02], but less platelet inhibition. Patients on DAPT exhibited greater platelet inhibition compared to either group [23.7 (±26.9) vs. 31.0 (±28.3) vs. 42.2 (±31.2); P < 0.01]. Patients who experienced MALE were more likely to be on DOAC therapy [43.8% vs. 22.0% P = 0.02]. Thromboelastography with platelet mapping analysis from patients who experienced MALE also demonstrated longer R-time [8.6 (±3.9 vs. 7.3 (±3.0); P = 0.05] and increased maximum clot amplitude (MA) [66.7 (±4.2) vs. 61.8 (±8.2); P = 0.001]. CONCLUSIONS: Direct oral anticoagulant therapy resulted in a prolonged R-time but had no impact on platelet inhibition. Patients who experienced MALE were more often on DOACs and demonstrated an increased R-time, but also showed greater platelet reactivity evident by increased MA, suggesting DOACs may not be effective at protecting against MALE. Further research comparing DOAC therapy to a DAPT approach may add clarity to emerging multimodal antithrombotic recommendations.

Outcomes of symptomatic penetrating aortic ulcer and intramural hematoma in the endovascular era.

BACKGROUND: Although endovascular technology has resulted in a paradigm shift in treatment, medical management remains the standard of care for penetrating aortic ulcer (PAU) and intramural hematoma (IMH). This study aimed to detail the short- and long-term outcomes of symptomatic PAU/IMH. METHODS: Institutional data on symptomatic PAU/IMH were gathered (2005-2020). The primary outcome was the composite of recurrent symptoms, radiographic progression, intervention, rupture, and death from related or unknown cause. Factors associated with the primary outcome were determined using a Fine-Gray model with death from an unrelated cause as a competing risk. RESULTS: A total of 83 symptomatic patients treated with medical management aside from ruptures and type A dissections: 21 isolated PAU, 30 isolated IMH, and 32 IMH and PAU. Adverse outcomes included symptom recurrence in 14 (16.9%), radiographic progression to dissection or saccular aneurysm in 17 (20.5%), surgery in 20 (24.1%) (17 thoracic endovascular aortic repair, 1 endovascular aortic repair, 1 frozen elephant trunk, and 1 open repair), and rupture in 4 (4.8%). Twenty-seven patients (32.5%) died during follow-up: 6 from IMH treatment complications, 8 from an unknown cause, and 13 from other causes. The 30-day, 1-year, and 5-year cumulative incidences of the primary outcome was 26.5% (95% confidence interval [CI], 16.9%-37.0%), 44.9% (95% CI, 32.8%-56.2%), and 57.5% (95% CI, 42.4%-69.9%), respectively. IMH with PAU was associated with a significantly higher risk of the primary outcome compared with isolated IMH (subdistribution hazard ratio, 2.21; 95% CI, 1.09-4.50; P = .027) and isolated PAU (subdistribution hazard ratio, 3.58; 95% CI, 1.44-8.88; P = .006). CONCLUSIONS: Complications from symptomatic PAU and IMH are frequent, with intervention, recurrent symptoms, radiographic progression, rupture, or death affecting 25% of patients at 30 days after diagnosis and almost one-half of patients 1 year after diagnosis. Given the high rate of adverse events in this population, investigation into a more aggressive interventional strategy may warranted, especially in patients with a combined IMH and PAU.

Atorvastatin Effect on Clopidogrel Efficacy in Patients with Peripheral Artery Disease.

BACKGROUND: Both clopidogrel and atorvastatin metabolism are rooted in hepatic cytochrome p450 activation. There are published reports of atorvastatin interfering with clopidogrel metabolism by inhibiting the activation of clopidogrel. This in turn would decrease the therapeutic effect of clopidogrel potentially resulting in an increase in thrombotic events in patients who are taking both medications. The emergence of viscoelastic assays, such as Thromboelastography with platelet mapping (TEG-PM), has been utilized to identify prothrombotic states and may provide insight into a patient's microvascular coagulation profile. The aim of this prospective, observational study was to delineate the differences in platelet function between patients on clopidogrel alone versus those on clopidogrel and atorvastatin in patients that are undergoing peripheral revascularization. METHODS: All patients undergoing revascularization between December 2020 and August 2022 were prospectively evaluated. Patients on clopidogrel and atorvastatin were compared to those on clopidogrel alone. Serial perioperative TEG-PM analysis was performed up to 6 months postoperatively and the platelet function in terms of percent inhibition was evaluated in both groups. Statistical analysis was performed using unpaired t-test to identify differences in platelet function. RESULTS: Over the study period, a total of 182 patients were enrolled. Of this cohort 72 patients met study criteria. 87 samples from the 72 patients were analyzed. 31 (43.05%) patients were on clopidogrel alone and 41 (56.94%) were on clopidogrel and atorvastatin. Patients on clopidogrel alone showed significantly greater platelet inhibition compared to those on clopidogrel and atorvastatin [49.01% vs. 34.54%, P = 0.03]. There was no statistical difference in platelet inhibition between groups in terms of aspirin use alone versus aspirin and atorvastatin. CONCLUSIONS: Patients on clopidogrel and atorvastatin showed significantly less platelet inhibition compared to those on clopidogrel alone, supporting the concept that atorvastatin may interfere with the therapeutic effect of clopidogrel. Patients taking atorvastatin may require an alternative antiplatelet therapy regimen that does not include clopidogrel to achieve adequate thromboprophylaxis.

Perceptions of General Surgery Program Leadership and Residents on Research Sabbatical.

INTRODUCTION: The incorporation of a 1-y- or 2-y research period during general surgery residency is increasingly common in many academic programs, yet often, it is heterogeneously structured and ill-defined. This survey-based observational study aimed to characterize the perceptions of general surgery program directors (PDs) and residents regarding an in-training, dedicated research sabbatical. METHODS: Two surveys were conducted using Qualtrics software. One survey was sent to general surgery residency PDs, and the other was sent to general surgery residents currently on a research sabbatical. The primary aim of the survey was to assess the PDs' and research residents' perceptions of the research sabbatical. RESULTS: Seven hundred and fifty-two surveys were analyzed, of which 120 were from PDs and 632 from research residents. Among the residents, 44.1% felt that the research time delayed their surgical training. Regarding research funding, 46.7% of the responding residents said that their residency program funded their research, 30.9% said they acquired funding independently, and 19.1% said that it came from a combination of residency program and independent funding. Finally, regarding how residents found their research opportunity, 42.7% said they found it independently and 53.3% said their program provided it. CONCLUSIONS: Research sabbaticals during residency may be considered essential to academic development. However, in this survey-based study, perceptions of research time and its structure varied greatly between PDs and residents. An intentional push toward developing guidelines for research sabbaticals may benefit residency program leadership and residents.

Variance in management of extracorporeal membrane oxygenation-associated fibrin sheaths at a single institution.

Objective: Extracorporeal membrane oxygenation (ECMO) support for patients with cardiac or respiratory failure has been increasingly used by advanced critical care practitioners. The thromboembolic complications of ECMO have been extensively discussed and researched; however, research and discussion on the development, risks, and management of cannulae-associated fibrin sheaths are lacking. Methods: Institutional review board approval was not required. We have presented three cases detailing the identification and individualized management of ECMO-associated fibrin sheaths at our institution. The three patients provided written informed consent for the report of their case details and imaging studies. Results: Of our three patients with ECMO-associated fibrin sheaths, two were managed successfully with anticoagulation alone. One could not receive anticoagulation therapy and underwent inferior vena cava filter placement. Conclusions: Fibrin sheath formation around indwelling ECMO cannulae is an unresearched complication of ECMO cannulation. We would recommend an individualized approach to the management of these fibrin sheaths and have provided three examples of successful management.

Peripheral artery disease and extracorporeal membrane oxygenation: Examining a high-risk cohort over time.

OBJECTIVE: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a resource-intensive approach for the management of refractory cardiogenic shock. Within this population exists a substantial cohort of patients with peripheral artery disease (PAD), which independently increases the risk of complications and all-cause mortality. We studied 10-year national trends of the impact of PAD among VA-ECMO recipients to better understand the prevalence of PAD and implications on outcomes in this vulnerable population. METHODS: This 10-year retrospective, propensity score-matched study identified all adult patients (≥18) who underwent VA-ECMO between 2009 and 2018, from a large US database (National Inpatient Sample). Patients with an ICD diagnosis of PAD were identified. The primary endpoints of in-hospital mortality, bleeding complications and major limb loss (above- or below-knee amputation) were compared between patients with PAD to those without. RESULTS: A total of 6768 patients were identified, of which 342 (5.3%) had PAD. The median age at admission was significantly higher in PAD patients [64 years vs. 55 years; p < .01], as was male gender [71% vs. 64%; p < .01]. Patients with PAD had higher rates of smoking (38.9% vs. 23.3%), hypertension (71.1% vs. 50%), diabetes (37.4% vs. 27.0%), chronic kidney disease (30.1% vs. 18.0%), coronary artery disease (76.0% vs. 35.0%) and dyslipidemia (76.0% vs. 35.0); all p < .01. After propensity-matching 2:1 for comorbidities, PAD patients were found to have significantly greater overall complications, including in-hospital mortality, bleeding, surgical wound infections, pseudoaneurysms, and major adverse limb events [71.9% vs. 63.9%; p < .01]. Subgroup analysis revealed greater in-hospital mortality [62.2% vs. 55.3%; p < .05], major amputations [4.1% vs. 0.3%; p < .01] and blood transfusions [32.2% vs. 26.2%; p < .05] in PAD patients. Over 2014-2018, the non-PAD group demonstrated statistically discernable trends in a 51.1% decrease in overall complications and a 28.1% increase in survival to discharge (all p < .01). Over the same time period the PAD cohort experienced a modest, nonsignificant, decrease in complications [7.0%, p = .40] and a decrease in those surviving to discharge [47.1% vs. 40.5%, p = .91]. CONCLUSION: Patients with PAD on VA-ECMO are sicker at baseline and experience significantly greater major amputations and higher in-hospital mortality. They have not benefitted from the considerable decrease in complication rates and increase in survival to discharge over time as compared to their non-PAD counterparts. These findings demonstrate the substantial frailty of the PAD population within an already high-risk cohort, and highlight the need for better procedural approaches and innovative technologies.

Factors Influencing Hospital Readmission after Lower Extremity Bypass for Chronic Limb-Threatening Ischemia.

Objectives: Unplanned hospital readmission is a leading source of hospital resource expenditure, and preventing readmission may improve both patient quality of life and healthcare costs. The factors influencing hospital readmission after lower extremity bypass (LEB) for chronic limb-threatening ischemia (CLTI) remain incompletely investigated. Methods: A regional, multi-institutional database was retrospectively reviewed for all patients who underwent LEB for CLTI between 1995 to 2020. The primary outcome was unplanned hospital readmission up to 30 days following bypass. Results: A total of 1315 patients underwent LEB across all institutions, of whom 843 (64.1%) underwent bypass for CLTI. The 30-day hospital readmission rate was 25.3%, and the leading causes of readmission were wound-related complications (51.6%). There was no difference in age, sex, or race between readmitted and non-readmitted patients. Conduit type and bypass target were also similar between groups. Readmitted patients more frequently underwent LEB for tissue loss (58.2% vs 50.2%, P = 0.042). On multivariable analysis, wound infection (odds ratio [OR] 9.1, 95% confidence interval [CI] 6.2-13.2, P < 0.001) and non-infectious wound complications (OR 2.0, 95% CI 1.0-3.9, P = 0.041) were independently associated with hospital readmission. Factors not associated with hospital readmission included patient age, conduit type, distal bypass target, and other medical comorbidities. Conclusions: One quarter of patients are readmitted within 30 days following lower extremity bypass for chronic limb-threatening ischemia. Efforts to mitigate wound infection and non-infectious wound complications may decrease rates of unplanned hospital readmission.

Variability of antiplatelet response in patients with peripheral artery disease.

OBJECTIVE: Antiplatelet therapy has been a pillar of management for peripheral artery disease (PAD). However, a significant subset of patients with PAD will be resistant to certain antiplatelet medications and, therefore, have an increased risk of graft and/or stent thrombosis unknown to the surgeon. At present, no point-of-care testing to identity which patients will experience benefit from these medications has been incorporated into the treatment guidelines. Thromboelastography with platelet mapping affords an opportunity to evaluate real-time coagulation dynamics and platelet function. In the present prospective, observational study, we aimed to delineate the variation in response to antiplatelet therapy in patients with PAD undergoing revascularization. METHODS: All patients who were undergoing named vessel revascularization during December 2020 through April 2022 were prospectively enrolled. Platelet mapping assays were performed in three clinical phases: preoperative, postoperative inpatient, and postoperative outpatient. The distribution of platelet reactivity within patients receiving mono- vs dual antiplatelet therapy was assessed, and a between-group inferential analysis was performed. The effect of comorbidities and intervention subtype on platelet inhibition was also analyzed. RESULTS: A total of 521 platelet mapping samples from 143 individual patients were analyzed using thromboelastography with platelet mapping. We found wide variability in the distribution of platelet inhibition, with a range of 0 to 100 and an interquartile range of 37.6. Although platelet inhibition with clopidogrel 75 mg was higher on average (44.8 ± 30.2) than that with aspirin 81 mg (24.6 ± 23.7) or aspirin 325 mg (27.1 ± 26.4; P = .001), clopidogrel at 75 mg demonstrated the highest variability in response. CONCLUSIONS: These data have demonstrated significant variability in the response to both mono- and dual antiplatelet therapy in PAD patients undergoing lower extremity revascularization. Future research on the effect of this variability in response on the clinical outcomes could provide invaluable understanding of the perioperative thrombotic risk.

Identifying Sex Dimorphism in Peripheral Artery Disease with Platelet Mapping.

BACKGROUND: Clinical outcomes in women with peripheral artery disease (PAD) after revascularization procedures are worse compared to men, yet there is little in the existing literature as why this may be the case. Platelet Mapping is an emerging point-of-care viscoelastic technology that measures the comprehensive properties of a blood clot, including fibrin-platelet interactions. This prospective observational study aimed to characterize the clinical and Platelet Mapping profiles of female and male patients undergoing lower extremity revascularization, and to correlate Platelet Mapping distribution to thrombotic potential. METHODS: All patients with a diagnosis of PAD undergoing named vessel open or endovascular revascularization to re-establish inflow, outflow, or both, during December 2020 and January 2022 were prospectively included. Patients were followed clinically for thrombosis for up to 1 year. Platelet Mapping assays were performed in 3 clinical phases: preoperative, postoperative inpatient, and postoperative outpatient. Inferential analysis between female and male patient was performed. The quartile distribution of Platelet Mapping metrics associated with thrombosis was used to infer to thrombotic potential. RESULTS: One hundred seven patients were enrolled, of which 37 (34.6%) were female. Female patients had significantly lower rates of uncontrolled diabetes (2.7% vs. 18.6%), hypertension requiring combination therapy (37.8% vs. 58.6%), chronic kidney disease (27.0% vs. 51.4%), coronary artery disease (29.7% vs. 57.1%), and myocardial infarction (16.2% vs. 35.7%) (all P < 0.05). Platelet reactivity was significantly higher in female patients with greater platelet aggregation (75.9 ± 23.3 vs. 63.5 ± 28.8) and lower platelet inhibition (23.8 ± 23.4 vs. 36.8 ± 28.9) (all P < 0.01). This trend was consistent over time when stratified by the postoperative inpatient and postoperative outpatient clinical phases. There was no statistically discernible difference in the use of antiplatelet therapy between groups, yet female patients continued to exhibit greater platelet reactivity when analyzed by the type of pharmacologic regimen (platelet aggregation on mono-antiplatelet therapy: 80.6 ± 21.0 in women versus 69.4 ± 25.0 in men; platelet aggregation on dual antiplatelet therapy: 67.9 ± 23.8 in women versus 44.8 ± 31.8 in men) (all P < 0.01). Twenty-one patients experienced postoperative graft/stent thrombosis within the study period. In relation to the overall study population, patients with thrombosis had Platelet Mapping metrics above the 50th percentile of overall platelet aggregation distribution. CONCLUSIONS: There is a growing appreciation for the differences in etiology, disease progression, and outcomes of cardiovascular conditions as they relate to sex. In this cohort, traditional cardiovascular risk factors were in lower prevalence in female patients. Platelet reactivity was found to be higher across clinical phases and antiplatelet regimens. High platelet reactivity was also associated with an increased incidence of thrombosis after lower extremity revascularization. These hypothesis-generating findings provide the basis for further exploration of sex-specific coagulation profiling in PAD patients.

Impact of socioeconomic disparities on major lower extremity revascularization complications.

INTRODUCTION: Low socioeconomic status (SES), distance lived from hospital, and insurance status are well documented in the literature to increase the risk of post-operative morbidity and mortality for some disease processes however there is a paucity of data regarding how this association impacts patients with peripheral artery disease (PAD). This study aimed to evaluate if SES, distance lived from hospital, and insurance status increased the risk of developing major graft failure in patients undergoing revascularization procedures for symptomatic PAD in a prospective, observation study. METHODS: In this prospective, observational study, all patients undergoing lower extremity revascularization (endovascular or open) were included from December 2020 to February 2022. Demographic factors, insurance status, operative details, and median income and distance from hospital were documented through chart review. Complications were defined as thrombosis/occlusion of the revascularized vessel or bypass graft or infection of the distal wound or surgical incision wound. Univariate and multivariate analysis were performed comparing patients that developed complications and those that did not. This project was undertaken at the Massachusetts General Hospital and was governed by the Institutional Review Board (IRB: 2020P000263) all patients agreed to participation via informed written consent prior to enrollment in the study. RESULTS: A total of 108 patients were enrolled in the study of which 94 underwent successful revascularization procedures. Of those 94 patients, 38 (40.4%) underwent open bypass, 39 (41.5%) underwent endovascular revascularization, and 17 (18.1%) underwent a hybrid approach. There were no significant differences in post-operative outcomes between operative approaches. Twenty-five patients (28.7%) experienced major revascularization complications as defined as re-occlusion of the treated vessel/thrombosis of the bypass graft (n = 13) or development of post-operative infection (n = 12). There was no significant difference in median income ($75,295 vs $87,757, p = NS), distance lived from hospital, (27.4 miles vs. 29.7 miles, p = NS), or type of insurance (private 24% vs 26%, government 76% vs 73%, p = NS between patients that experienced complications versus those that did not have complications. These findings suggest the risk of major graft failure is independent of a patient's socioeconomic status, distance lived from hospital, or insurance type in patients undergoing revascularization procedures for PAD. CONCLUSION: While socioeconomic factors impact access to and have a known association with negative outcomes, complications in patients with PAD appear to be independent of these factors. To mitigate the negative outcomes in patients with peripheral artery disease, a focus should be on patient risk factors and modifiable medical factors that contribute to adverse outcomes.

Multi-institutional outcomes after femoropopliteal bypass in octogenarians.

OBJECTIVES: Open lower extremity revascularization is controversial among octogenarians; however, the indications for surgical bypass are higher in the elderly population. The aim of the study was to compare postoperative outcomes between octogenarians and non-octogenarians following femoropopliteal bypass surgery. METHODS: Our regional, multi-institutional database was queried for femoropopliteal bypass procedures performed between 1995 and 2020. Electronic medical records were individually reviewed for operative and postoperative data. Univariable and multivariable logistic regression were utilized to determine predictors of postoperative outcomes. RESULTS: Among 1315 patients who underwent femoropopliteal bypass, 234 (17.8%) were octogenarians. Octogenarians more frequently underwent bypass for lower extremity tissue loss (48.7% vs 30.2%), whereas claudication was more common among non-octogenarians (24.0% vs 9.8%) (p < .001). Below-knee bypass target (72.2% vs 59.3%) and prosthetic conduit utilization (58.5% vs 43.7%) were more frequent in octogenarians (p < .001 each). Overall hospital length of stay was longer among patients > 80 years (median 6 days [interquartile range [IQR] 4-9] vs 5 days [IQR 4-8], p = .017). The overall 30-day (5.6% vs 1.5%) and one-year mortality rates (25.6% vs 7.9%) were higher among octogenarians (p < .001 each). On multivariable analysis, age greater than 80 years was found to be an independent risk factor for postoperative mortality (OR 3.79 [1.75-8.20], p = .0007). CONCLUSIONS: Octogenarians undergoing bypass femoropopliteal bypass surgery have considerably worse postoperative outcomes, compared with non-octogenarians. These data may help inform elderly patients prior to undergoing open lower extremity revascularization.

Outcomes of Femoropopliteal Bypass for Lifestyle-Limiting Claudication in the Endovascular Era.

INTRODUCTION: Outcomes after femoropopliteal bypass for intermittent claudication (IC) remain unclear in the endovascular era. METHODS: A multi-institutional database was retrospectively queried for all femoropopliteal bypass procedures performed between 1995 and 2020. Demographics, operative details, and outcomes were documented. A statistical analysis included Kaplan-Meier curves and Cox proportional hazards ratios (HR). RESULTS: A total of 282 patients underwent femoropopliteal bypass surgery for IC. Median age was 68 y (interquartile range, 61-73 y). Bypass conduits included great saphenous vein (GSV) (48.2%), prosthetic grafts (48.9%), and non-GSV autogenous grafts (2.8%). Distal bypass target was above-knee in 62.1% and below-knee in 37.9% of patients. The most common postoperative complications were wound infections (14.2%) followed by unplanned 30-d hospital readmissions (12.4%). Mortality rates were low at 0.4% (30 d) and 3.2% (1 y). Five-year primary patency rates trended highest for claudicants undergoing above-knee bypass with GSV conduit (log-rank P = 0.065). Five-year amputation-free survival rates were highest using GSV conduit regardless of distal bypass target (log-rank P = 0.017). On a multivariable analysis, age (HR 1.02 [1.00-1.04], P = 0.023) and active smoking (HR 1.48 [1.06-2.06], P = 0.021) were identified as risk factors for diminished primary graft patency. Risk factors for amputation-free survival included age (HR 1.03 [1.01-1.05], P < 0.001) and GSV conduit type (HR 0.65 [0.46-0.90], P = 0.011). CONCLUSIONS: Femoropopliteal bypass among claudicants is associated with high rates of wound infection and hospital readmission. Active smoking portends worse outcomes in this population. These data may inform clinical decision-making regarding surgical intervention for claudication in the endovascular era.

A comprehensive review on antithrombotic therapy for peripheral artery disease.

Peripheral artery disease (PAD) is a morbid and costly disease that can result in loss of limb and life if not managed appropriately with risk factor modification, antithrombotic therapy, and revascularization when necessary. Antithrombotic therapy includes antiplatelet and anticoagulant drugs. Antiplatelet agents used in PAD can include aspirin, reversible and irreversible P2Y12 inhibitors, and PAR-1 antagonists. These drugs are prescribed as both monotherapy or dual-antiplatelet therapy and are critical components of pre- and post-revascularization maintenance. Anticoagulants, such as vitamin K antagonists and heparin products, have long been used in cardiac disease; in patients with PAD, these drugs have been largely supplanted by new direct factor Xa antagonists, which offer superior safety profiles and reduced adverse events after revascularization. Anticoagulants are often used alongside antiplatelet medications after PAD revascularization; however, there is a lack of guideline consensus about therapy selection and large regional disparity in regard to antithrombotic prescribing patterns. In this review, we analyze the existing literature and guidelines regarding the use of antithrombotic therapy in patients with PAD and offer a framework to aid clinicians' decision making regarding therapy selection and duration based on current existing evidence.

Impact of anticoagulation/antiplatelet therapy on femoropopliteal bypass graft outcomes.

BACKGROUND: Anticoagulant and antiplatelet (AC/AP) medications have been reported to improve bypass graft patency, however, the optimal AC/AP strategy remains unclear in the heterogenous peripheral artery disease population. METHODS: A multi-institutional retrospective review utilizing the Research Patient Data Registry database from 1995 to 2020 was performed for all patients who underwent femoropopliteal bypass procedures. Electronic medical records were used to obtain demographic information, comorbidities, smoking status, operative details (bypass target), postoperative AC/AP medications, postoperative complications, and long-term outcomes and were reviewed for the cohort. Cox proportional hazards model was used to determine independent risk factors for major adverse limb events (MALE) after bypass. MALE was defined as reintervention for patency or major amputation of index limb (above- or below-knee amputation). RESULTS: A total of 1421 patients underwent femoropopliteal bypass between 1995 and 2020 throughout five institutions included in this study. Complete data were available for 1292 of the 1421 patients (90.9%). The indications for bypass included intermittent claudication (21.4%), rest pain (30.3%), tissue loss (33.5%), and nonatherosclerotic disease (14.8%). Distal bypass targets comprised above-knee (38.6%) and below-knee (61.4%) popliteal arteries. Patients were divided into six groups based on postoperative AC/AP use including none (n = 57 [4.4%]), monoantiplatelet therapy (n = 587 [45.4%]), dual AP therapy (n = 214 [16.6%]), AC alone (n = 73 [5.7%]), AC + monoantiplatelet therapy (n = 319 [24.7%]), and AC + dual AP therapy (n = 42 [3.3%]). Postoperative bleeding complications were low for both hematoma (3.7%) and pseudoaneurysm (0.7%). There was no difference in bleeding complications across AC/AP groups (hematoma, P = .61; pseudoaneurysm, P = .31). After adjusting for patient factors, below-knee bypass target (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.04-1.52; P = .019) and bypass for tissue loss (HR, 1.40; 95% CI, 1.04-1.88; P = .028) were independent predictors for MALE. Great saphenous vein conduit trended toward protection for MALE, compared with prosthetic grafts (HR, 0.84; 95% CI, 0.70-1.01; P = .06). No AC/AP regimen was associated with of MALE, even stratifying by above-knee and below-knee bypass cohorts. The median follow-up period was 2 years. CONCLUSIONS: Among patients undergoing femoropopliteal bypass grafting, no combination of AC or AP medications was associated with improved graft patency; however, a below-knee target and tissue loss were associated with adverse limb events. AC and AP regimen may be individualized after bypass with regard to other concomitant medical comorbidities.

Utilization of Thromboelastography with Platelet Mapping to Predict Infection and Poor Wound Healing in Postoperative Vascular Patients.

BACKGROUND: Postoperative infection and wound dehiscence rates are higher than expected in peripheral artery disease and contribute significantly to limb loss and mortality. Microvascular pathology characterized by microthrombi and increased platelet aggregation have been cited as contributing factors to poor wound healing and infection. The emergence of viscoelastic assays, such as thromboelastography with platelet mapping (TEG-PM), have been utilized to identify prothrombotic states and may provide insight into a patient's microvascular coagulation profile. This prospective, observational study aimed to determine if TEG-PM could predict poor wound healing or infection following lower extremity revascularization. METHODS: All patients undergoing revascularization between December 2020 and January 2022 were prospectively included and followed for wound complications or non-surgical site infections of the index limb. TEG-PM metrics at the first postoperative follow-up in the nonevent group was compared to the TEG-PM sample preceding the diagnosis of infection/dehiscence in the event group. Cox proportional hazards (PH) regression was used to model the predictive value of viscoelastic parameters. Cut-point analysis to determine high-risk groups was determined by performing receiver operating characteristic curve analysis. RESULTS: Of the 102 patients, 18.6% experienced infection/dehiscence. The TEG-PM sample analyzed in the event group was, on average, 19.5 days prior to the diagnosis of an event. The event group had significantly higher maximum clot amplitude (MA) (47.3 mm ± 16.0 vs. 30.6 mm ± 15.3, P < 0.01), higher platelet aggregation (71.3% ± 27.7 vs. 31.2% ± 24.0, P < 0.01), and lower platelet inhibition (28.7% ± 27.7 vs. 68.7% ± 24.1, P < 0.01). Cox PH analysis identified platelet aggregation as an independent and consistent predictor of infection (hazard ratio = 1.04, 95% confidence interval 1.03-1.06, P < 0.01). An optimal cut-point of > 33.2 mm MA, > 46.6% platelet aggregation, or < 55.8% platelet inhibition identifies those with infection/dehiscence with 79.0-89.5% sensitivity. CONCLUSIONS: These are the first data to provide a quantitative link between prothrombotic viscoelastic coagulation profiles with the development of infection/dehiscence. Based on the cut-points of > 33.2 mm MA, > 46.6% platelet aggregation, or < 55.8% platelet inhibition, we recommend consideration of an enhanced antimicrobial or antithrombotic approach for these high risk groups.

Risk factors and consequences of graft infection after femoropopliteal bypass: A 25-year experience.

OBJECTIVE: In this multi-institutional series, we aimed to determine the incidence, risk factors, and long-term outcomes of graft infection in patients post-femoropopliteal bypass. METHODS: A multi-institutional database was retrospectively queried for all femoropopliteal bypass procedures from 1995 through 2020. Cumulative incidence function estimated the long-term rate of bypass graft infection (BGI), and the Fine-Gray model was used to determine independent risk factors for BGI to account for death as a competing risk. RESULTS: Over the 25-year period, 1315 femoral popliteal bypasses were identified with a median follow-up of 2.89 years (interquartile range, 0.75-6.55 years). BGI was diagnosed in 34 patients (2.6%). BGI occurred between 9 days and 11.2 years postoperatively, with a median of 109 days. Estimated 1- and 5-year incidence of BGI was 2.1% (95% confidence interval [CI], 1.4%-3.1%) and 2.8% (95% CI, 1.9%-3.9%), respectively. Medical comorbidities, indications for bypass, and popliteal bypass targets (above- vs below-knee) were similar between patients with BGI and all patients (P = not significant for each). Patients with BGI were more frequently complicated by postoperative hematoma (14.7% vs 3.7%), superficial wound infection (38.2% vs 19.2%), lymphocele/lymphorrhea (8.8% vs 2.1%), and 30-day readmission rates (47.1% vs 21.3%) (P < .05 for each). Most commonly isolated pathogens were Staphylococcus aureus (n = 19; 55.9%) and polymicrobial cultures (n = 5; 14.7%). Reoperation for BGI involved incision and drainage (n = 7; 20.6%), graft excision without reconstruction (n = 12; 35.3%), graft excision with in-line reconstruction (n = 11; 32.4%), and graft excision with extra-anatomic reconstruction (n = 2; 5.9%). Nine patients with BGI (26.5%) ultimately required major amputation. Prosthetic bypass (subdistribution hazard ratio [SHR], 3.73; 95% CI, 1.64-8.51; P = .002), postoperative hematoma (SHR, 3.44; 95% CI, 1.23-9.61; P = .018), and 30-day readmission (SHR, 2.75; 95% CI, 1.27-5.44; P = .010) were independently associated with BGI. One-year amputation-free survival was 50% (95% CI, 31.9%-65.7%) after BGI. CONCLUSIONS: BGI is a rare complication of femoral-popliteal bypass with significant morbidity. Graft infection is associated with the use of prosthetic grafts, postoperative hematoma, and unplanned hospital readmission. Mitigation of these risk factors may decrease the risk of this dreaded complication.